The objective is to characterize the biochemical and genetical mechanisms of obligate intracellular parasitism between the eukaryotic host and prokaryotic parasite. Molecular interactions at the cell surface and with soluble components are being investigated as primary determinants of metabolic cooperation between host and parasite. Unusual membrane functions have been discovered which contribute to the success of Rickettsia typhi as a scavenger of critical host components. We have discovered a major determinant of the Q fever agent, Coxiella burnetii, intravacuolar parasitism. Uptake of nutrients and metabolism by C. burnetii is higly dependent upon the hydrogen ion concentration of the phagolysosome which maintains a pH between 4.5 to 4.8. The acidophilic nature of C. burnetii may aid in the development of an axenic medium for the growth of this microoganism. This discovery will have a positive impact on future studies designed to delineate the mechanisms of pathogenicity of this medically important intracellular parasite as well as define an apparently unique response of an obligate intracellular parasite to host cellular defense mechanisms.